The recent FDA approval of the SPECT imaging agent I-123 labeled DaTscan for diagnosis and monitoring progression of Parkinson's Disease (PD) has open up a new era in SPECT brain imaging. Unlike with perfusion imaging where the entire brain is the volume of interest, with PD the structures of interest are the putamen and caudate (and potentially substantia nigra) which lie in the interior portion of the brain. However imaging of the occipital lobe is also required with PD for calculation of the striatal binding rati (SBR), a parameter of significance in the early diagnosis and differentiation of PD from other disorders with similar clinical presentations. Our hypothesis is that combining a specifically designed multi-pinhole (MPH) collimator on one detector head with a fan-beam collimator on the remaining head of current dual-headed SPECT systems, coupled with iterative reconstruction with modeling system spatial resolution, will result in improved detection and quantification of structures in the interior region of the brain at marginal cost (the price of collimator(s) and reconstruction software). The MPH collimator would be designed to provide enhanced spatial resolution / sensitivity for the interior of the brain. The fan-beam collimator would provide lower resolution but complete sampling of the brain addressing data sufficiency and allowing a volume-of-interest to be defined over the occipital lobe for calculation of SBR's. Clinically this would provide a low-cost system allowing improved visualization and relative quantification of function of structures in the interior region of the brain, potentially as small as the ~4 mm substantia nigra, which cannot currently be achieved by other than expensive, brain dedicated, SPECT systems. This would greatly impact the early detection and differentiation of PD, and possibly other neurological disorders as new SPECT imaging agents are approved. Our approach for further investigating our hypothesis is based on the initial exploration we have conducted under funding provided by NIH R21 EB016391 and is organized into five specific aims. The first specific aim is to complete the optimization of the MPH collimator design through task-based optimization for the tasks of detection using the Channelized Hotelling Observer (CHO) and quantification of striatal function by calculation of the SBR. The second specific aim is to finish development of inclusion of MPH system geometry and response in reconstruction. The third specific aim is to have our colleagues at the Center for Gamma Ray Imaging (CGRI) at the University of Arizona construct the MPH. The fourth specific aim is to install and test the combined fan-beam and MPH system on a SPECT/CT camera using phantoms. Our fifth specific aim is to image five patients with the combined system.